OBJECTIVES: A. The overall objectives of the project include determination of DNA damaging, cytotoxic and genetic effects in mitosis and gametogenesis of bleomycin-phleomycin group antibiotics (BM-PM), and other anticancer drugs. The long-term objective is to determine molecular bases for in vivo activities. B. Goals for the current year, using Saccharomyces cerevisiae: 1. Using the technique of alkaline sucrose DNA sedimentation, determine dependence of measurable DNA damage by BM on selected alterable conditions of pregrowth, treatment and posttreatment incubation of cells. 2. Measure dose-dependent DNA damage by bleomycin in normal and selected mutant strains. Determine if damage is repairable in these strains. 3. Test the hypothesis that mutants defective in their ability to excise UV-induced pyrimidine dimers in DNA are more resistant than normal strains to cell killing by bleomycin-phleomycin group antibiotics. 4. Determine cell-cycle phase dependency of BM effects on cell killing and DNA damage. 5. Determine dose-dependent cytotoxic and genetic responses of growing cells to misonidazole (RO58-2), considered a potential radiosensitizer in cancer therapy in combination with radiation. 6. Revive, retest and characterize mutants altered in their resistance to cell killing by bleomycin. 7. Adapt the technique of alkaline elution of DNA from cell lysates, successfully used for studies of DNA from mammalian cells, for studies of DNA from yeast cells.